The purpose of this mentored patient-oriented research career development award (K23) is to assist Alex Manini, MD to become an independent research scientist in drug overdose emergencies. Guided by Dr. David Vlahov (mentor), he will collaborate with accomplished investigators to study adverse cardiovascular events (ACVE) in drug overdose, building upon exciting preliminary data. Training activities include courses in statistics and epidemiology at the Columbia Mailman School of Public Health;the Addiction Training program at Mount Sinai School of Medicine;focused mentorship in drug overdose, epidemiology, and cardiology;and presentation of interim results at regional, national, and international conferences. Proposed is a prognostic indicator study of emergency department patients with drug overdose to evaluate occurrence of in-hospital ACVE. Based on preliminary data, the hypothesis is that clinical risk factors (e.g., demographics, exposure intent, electrocardiogram) will independently predict in-hospital ACVE. The specific aims are: (1) to determine the incidence of ACVE in patients with drug overdose;(2) to identify prognostic indicators for in-hospital ACVE in patients with drug overdose;and (3) to derive a simple risk stratification scoring system based on the above prognostic indicators for ACVE and to test the diagnostic characteristics of the risk score to aid clinical decision-making for patients with acute drug overdose. To meet these aims, emergency department patients with drug overdose at two urban teaching hospitals will be prospectively enrolled and followed longitudinally for occurrence of in-hospital ACVE. Overdose severity will be assessed with Poison Severity Scores, Acute Physiology and Chronic Health Evaluation, and adjudicated ACVE endpoints. Interpretation of the admission electrocardiogram will be performed by a blinded cardiologist, and serum will be evaluated for toxicology screens and cardiac biomarkers. Prognostic indicators for ACVE will be derived and incorporated into a simple risk score with a cutpoint chosen to achieve optimal diagnostic test characteristics. Implementation of this risk stratification tool has the potential to prevent AGVE complications for an estimated 1.5 million drug-related emergency department visits in the U.S. annually. PUBLIC HEALTH RELEVANCE: Drug overdose and prescription drug abuse affect diverse demographics, races/ethnicities, and economic classes. Poisoning is the second leading cause of injury-related fatality in the U.S., and the leading cause of cardiac arrest in victims under 40 years of age. There are 2.4 million reported poison exposures and approximately 1.5 million drug-related emergencies in the U.S. annually.